Genotype networks drive oscillating endemicity and epidemic trajectories in viral evolution

Abstract: Rapidly evolving viruses use antigenic drift as a key mechanism to evade host immunity and persist in real populations. While traditional models of antigenic drift and epidemic spread rely on low-dimensional antigenic spaces, genomic surveillance data reveal that viral evolution produces complex antigenic genotype networks with hierarchical modular structures. In this study, we present an eco-evolutionary framework in which viral evolution and population immunity dynamics are shaped by the structure of antigenic genotype networks. Using synthetic networks, we demonstrate that network topology alone can drive transitions between stable endemic states and recurrent seasonal epidemics. Furthermore, our results show how the integration of the genotype network of the H3N2 influenza in our model allows for estimating the emergence times of various haplotypes resulting from its evolution. Our findings underscore the critical role of the topology of genotype networks in shaping epidemic behavior and, besides, provide a robust framework for integrating real-world genomic data into predictive epidemic models.